Biomarkers for immunotherapy response in head and neck cancer

Preclinical data suggest that head and neck squamous cell carcinoma (HNSCC) is a profoundly immunosuppressive disease, characterized by abnormal secretion of proinflammatory cytokines and dysfunction of immune effector cells. Based on landmark phase III trials, two anti-Programmed Cell Death-1 (PD-1) antibodies, pembrolizumab and nivolumab have been approved for HNSCC by FDA and EMEA in the recurrent/metastatic setting; in addition, pembrolizumab has recently received FDA and EMEA approval as first line treatment. In clinical practice, only a minority of patients with HNSCC derive benefit from immunotherapy and the need for the discovery of novel biomarkers to optimize treatment strategies is becoming increasingly more relevant. Although currently only PD-L1 is widely used as a predictive biomarker for response to immune checkpoint inhibitors in HNSCC, there are many ongoing trials focusing on the identification of new biomarkers. This review will summarize current data on emerging biomarkers for response to immunotherapy in HNSCC.